FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4365512191> ?p ?o ?g. }

• W4365512191 endingPage "LB006" @default.
• W4365512191 startingPage "LB006" @default.
• W4365512191 abstract "Abstract Chromosomal translocations creating fusion genes are among the most common mutation class of known cancer genes, and they have long been identified as driver mutations in certain types of cancer. Recently, oncogenic fusion genes (oncofusions, OFs) have been found in many hematological and solid tumors, demonstrating that translocations are a common cause of malignancy. The frequency of recurrent gene fusions varies depending of the specific type of cancer, but currently identified translocations are estimated to drive up-to 20% of cancer morbidity. In many occasions the oncofusion is the sole driver of oncogenesis when present and certain oncofusion pairs are typically found in one or few specific cancers. ETV6-NTRK3 (EN) oncofusion, is a product of the chromosomal t(12; 15)(p13; q25) translocation, which fuses the N-terminal SAM (sterile alpha motif) domain of ETV6 to the C-terminal protein tyrosine kinase domain of NTRK3 (also known as TrkC). EN is expressed from the ETV6 promoter in the fused chromosome 15. The ETV6 promoter is generally more active, than NTRK3 promoter, and causes EN fusions to be expressed more highly in several tissues and especially in bone marrow and salivary glands. ETV6 forms fusions with many kinases, which are found in hematological malignancies and solid tumors. Except for ETV6-NTRK3, other ETV6-kinase fusions are reported in either hematological or solid malignancies and ETV6-NTRK3 further distinguishes itself by being also reported in several subtypes in both cases. Four EN variants with alternating break points have since been detected in a wide range of human cancers. To provide insight into EN oncogenesis, we employed a proximity labeling mass spectrometry approach to define the molecular context of the EN fusions. We identify 237 high-confidence interactors, which link EN fusions to several key signaling pathways, including ERBB, Insulin and JAK/STAT. We then assess the effects of EN variants on these pathways, and show that the pan NTRK inhibitor selitrectinib (LOXO-195) inhibits the oncogenic activity of EN2, the most common variant. This systems-level analysis of defines the molecular framework in which EN oncofusions operate to promote cancer. Citation Format: Matias Kinnunen, Xiaonan Liu, Kari Salokas, Salla Keskitalo, Markku Varjosalo. Interactome analysis identifies signaling pathways activated by ETV6-NTRK3 oncogenic gene fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB006." @default.
• W4365512191 created "2023-04-15" @default.
• W4365512191 creator A5016995592 @default.
• W4365512191 creator A5041458743 @default.
• W4365512191 creator A5054623923 @default.
• W4365512191 creator A5069375995 @default.
• W4365512191 creator A5088991911 @default.
• W4365512191 date "2023-04-14" @default.
• W4365512191 modified "2023-09-23" @default.
• W4365512191 title "Abstract LB006: Interactome analysis identifies signaling pathways activated by ETV6-NTRK3 oncogenic gene fusions" @default.
• W4365512191 doi "https://doi.org/10.1158/1538-7445.am2023-lb006" @default.
• W4365512191 hasPublicationYear "2023" @default.
• W4365512191 type Work @default.
• W4365512191 citedByCount "0" @default.
• W4365512191 crossrefType "journal-article" @default.
• W4365512191 hasAuthorship W4365512191A5016995592 @default.
• W4365512191 hasAuthorship W4365512191A5041458743 @default.
• W4365512191 hasAuthorship W4365512191A5054623923 @default.
• W4365512191 hasAuthorship W4365512191A5069375995 @default.
• W4365512191 hasAuthorship W4365512191A5088991911 @default.
• W4365512191 hasConcept C104317684 @default.
• W4365512191 hasConcept C111829193 @default.
• W4365512191 hasConcept C121608353 @default.
• W4365512191 hasConcept C123894998 @default.
• W4365512191 hasConcept C138626823 @default.
• W4365512191 hasConcept C150194340 @default.
• W4365512191 hasConcept C26260077 @default.
• W4365512191 hasConcept C2780833115 @default.
• W4365512191 hasConcept C40767141 @default.
• W4365512191 hasConcept C502942594 @default.
• W4365512191 hasConcept C54355233 @default.
• W4365512191 hasConcept C555283112 @default.
• W4365512191 hasConcept C86803240 @default.
• W4365512191 hasConceptScore W4365512191C104317684 @default.
• W4365512191 hasConceptScore W4365512191C111829193 @default.
• W4365512191 hasConceptScore W4365512191C121608353 @default.
• W4365512191 hasConceptScore W4365512191C123894998 @default.
• W4365512191 hasConceptScore W4365512191C138626823 @default.
• W4365512191 hasConceptScore W4365512191C150194340 @default.
• W4365512191 hasConceptScore W4365512191C26260077 @default.
• W4365512191 hasConceptScore W4365512191C2780833115 @default.
• W4365512191 hasConceptScore W4365512191C40767141 @default.
• W4365512191 hasConceptScore W4365512191C502942594 @default.
• W4365512191 hasConceptScore W4365512191C54355233 @default.
• W4365512191 hasConceptScore W4365512191C555283112 @default.
• W4365512191 hasConceptScore W4365512191C86803240 @default.
• W4365512191 hasIssue "8_Supplement" @default.
• W4365512191 hasLocation W43655121911 @default.
• W4365512191 hasOpenAccess W4365512191 @default.
• W4365512191 hasPrimaryLocation W43655121911 @default.
• W4365512191 hasRelatedWork W1605669962 @default.
• W4365512191 hasRelatedWork W2023217887 @default.
• W4365512191 hasRelatedWork W2049496060 @default.
• W4365512191 hasRelatedWork W2095898073 @default.
• W4365512191 hasRelatedWork W2095928029 @default.
• W4365512191 hasRelatedWork W2122038874 @default.
• W4365512191 hasRelatedWork W2618189922 @default.
• W4365512191 hasRelatedWork W3162475615 @default.
• W4365512191 hasRelatedWork W4244240117 @default.
• W4365512191 hasRelatedWork W4308180770 @default.
• W4365512191 hasVolume "83" @default.
• W4365512191 isParatext "false" @default.
• W4365512191 isRetracted "false" @default.
• W4365512191 workType "article" @default.